This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During embryonic development, nerve cells (or neurons) must stretch from their point of origin to reach their proper target in order to form the intricate, interconnected network of the nervous system. To accomplish this, neurons send out long, cable-like projections called axons. At the tip of growing axons is a motile, sensory structure called a growth cone. Growth cones are responsible for interpreting their extracellular environment to determine whether there is a better or worse direction for them to extend. Proper attraction of growth cones towards target cells and repulsion away from off-target cells is fundamentally important for correct nervous system development. This project is focused on understanding the molecular signaling pathways that control the shape and movement of neuronal growth cones in response to netrin-1, the first and one of the most important cues that guide axons during development of the central nervous system. Our work will define the interactions the cellular receptor for netrin-1 and the machinery that controls growth cone movement, and thus lend insight into the molecular mechanisms underlying axon guidance and neural development.